Staphylococcus aureus strain HMC3 isolated at the Hershey Medical Center, was resistant to vancomycin (VRSA) through the presence of the vanA resistance gene; it also contained mecA, erm(A), erm(B), tet(K) and aac(6')-aph(2"), conferring resistance to licensed beta-lactams, macrolides, tetracycline and aminoglycosides. HMC3 also had alterations in GyrA and GrlB and was resistant to available quinolones. Experimental drugs with low MICs (<2 mg/L) for VRSA HMC3 included cephalosporins BAL9141 and RWJ-54428; glycopeptides oritavancin and dalbavancin; the lipopeptide daptomycin; the glycolipodepsipeptide ramoplanin; new fluoroquinolones WCK 771 A, WCK 1153, DK-507k and sitafloxacin; and the DNA nanobinder GS02-02. These agents were all bactericidal as were trimethoprim/sulfamethoxazole and teicoplanin (MIC 4 mg/L). Oxazolidinones linezolid and ranbezolid; the injectable streptogramin quinupristin/dalfopristin; DNA nanobinders GS2-10547 and GS02-104; peptide deformylase inhibitors NVP-PDF713 and GS02-12; tetracycline derivative tigecycline; the antifolate iclaprim; mupirocin and fusidic acid were all active in vitro but bacteriostatic.

Resistance rates to amikacin, ciprofloxacin, ceftazidime, cefepime, imipenem, cefoperazone/sulbactam and piperacillin/tazobactam in Escherichia coli (n= 438), Klebsiella pneumoniae (n= 444), Pseudomonas aeruginosa (n= 210) and Acinetobacter baumanni (n=200) were determined with e-test in a multicenter surveillance study (Hitit-2) in 2007. ESBL production in Escherichia coli and K. pneumoniae was investigated following the CLSI guidelines. Overall 42.0% of E.coli and 41.4% of K. pneumoniae were ESBL producers. In E. coli , resistance to imipenem was not observed, resistance to ciprofloxacin and amikacin was 58.0% and 5.5% respectively. In K. pneumoniae resistance to imipenem, ciprofloxacin and amikacin was 3.1%, 17.8% 12.4% respectively. In P. aeruginosa the lowest rate of resistance was observed with piperacillin/tazobactam (18.1%). A. baumanni isolates were highly resistant to all the antimicrobial agents, the lowest level of resistance was observed against cefoperazone/sulbactam (52.0%) followed by imipenem (55.5%). this study showed that resistance rates to antimicrobials are high in nosocomial isolates and show variations among the centers.

The aims of this prospective study were to: (1) determine the rate of blood culture contamination; (2) describe and compare the epidemiologic, clinical and microbiological characteristics of hospital- and community-acquired bloodstream infections; and (3) determine the mortality resulting from bloodstream infections. The rate of true bacteremia was 12.1%, and 10.7% of cultures were contaminated. Of the 567 episodes of bloodstream infection, 73.4% were hospital-acquired, and 26.6% were community-acquired. The most commonly isolated microorganisms were staphylococci (44%, methicillin resistant 69.4%), enterococci (15%) and Escherichia coli (12.5%) in hospital-acquired episodes, and Brucella spp. (21.9%), E. coli (19.2%) and Staphylococcus aureus (14.6%, methicillin resistant 9.1%) in community-acquired episodes. While the overall mortality rate was 25.4%, death attributable to bloodstream infections was 16.6% in hospital-acquired episodes and 13.9% in community-acquired episodes. The highest mortality occurred in patients with bacteremia due to Pseudomonas aeruginosa (37.5%) in hospital-acquired episodes, and in patients with bacteremia due to Streptococcus pneumoniae (50%) in community-acquired episodes. Underlying diseases, severity of illness, presence of bladder catheter, previous use of antibiotics, tracheal intubation and adequacy of treatment were found to be significantly associated with death.

The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC 50 s/MIC 90 s (g/ml) against 131 Staphylococcus aureus strains (<0.002 to 2.0/0.06/0.5) and 128 coagulase-negative staphylococci (0.004 to 0.25/0.016/ 0.125). Among strains tested, 76 S. aureus strains and 51 coagulase-negative staphylococci were resistant to ciprofloxacin. DX-619 had the lowest MIC 50 /MIC 90 values against 127 quinolone-resistant staphylococci (0.125/0.5), followed by sitafloxacin (0.5/4), moxifloxacin (2/8), gatifloxacin (4/16), levofloxacin (16/>32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycinresistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 g/ml and sitafloxacin at 1.0 g/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 g/ml after <50 days of selection compared to 16 to >32 g/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4؋ MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including methicillin-, ciprofloxacin-, and vancomycin-resistant strains.The emergence of methicillin-and quinolone-resistant, and recently glycopeptide-intermediate, staphylococci, as well as the propensity of these organisms to cause serious systemic infections in immunocompromised hosts, necessitates other therapeutic modalities (2,9,10,19,24,29). During 2002, two clinical strains of vancomycin-resistant Staphylococcus aureus (VRSA) carrying vanA, one from Detroit, Mich., and one from our hospital, have been isolated (3, 28). Several months ago, a third VRSA was isolated in New York city (14).Most methicillin-resistant staphylococci are also resistant...